The objective specific to this Supplement to Grant TM 10451-11 is to perform parallel experiments analogous to those reported independently by three laboratoies, bearing directly on the mechanism or mechanisms of cooperative allosteric interactions. The conclusions reached among these laboratories are not always in accord. A property of some oligomeric allosteric regulatory enzymes is that of "negative cooperativity" or "anti-cooperatively" in ligand binding. This phenomenon is noteworthy since it can be utilized in experiments for differentiating among model allosteric mechanisms. Three laboratories have been particularly prominent in utilizing this phenomenon for distinguishing among microscopic allosteric mechanisms: Dr. Dan Koshland and his collaborators at the University of California at Berkely; Dr. Alex Levitzki and his collaborators at the Weizman Institute, Rehovot, Israel; and this laboratory. Somewhat different experiments on "negatively cooperative" systems have been carried out very recently in the three laboratories, with divergent conclusions. The "proper" conclusion is of considerable interest in protein chemistry at this time. Dr. Levitzki is planning to spend this summer lecturing and working with this former collaborator, Dr. Koshland, at Berkeley. This Supplement is for the purpose of extending Dr. Levitzki's visit in the United States through December, 1974, in order to carry out experiments in Eugene and to attempt to reconcile the differences in mechanistic interpretation which now exist. It should be pointed out that although there is considerable scientific disagreement among laboratories, there are very open exchanges of factual information and critical discussion. The situation is thus ideal for the reconciliation of the theories with experiments.